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Immune Suppression of Glia Maturation Factor Reverses Behavioral Impairment, Attenuates Amyloid Plaque Pathology and Neuroinflammation in an Alzheimer's Disease Mouse Model.
Journal of Neuroimmune Pharmacology ( IF 5.2 ) Pub Date : 2020-06-05 , DOI: 10.1007/s11481-020-09929-4
Mohammad Ejaz Ahmed 1, 2 , Govindhasamy Pushpavathi Selvakumar 1, 2 , Ramasamy Thangavel 1, 2 , Duraisamy Kempuraj 1, 2 , Sudhanshu P Raikwar 1, 2 , Smita Zaheer 1 , Shankar Iyer 1, 2 , Asgar Zaheer 1, 2
Affiliation  

Alzheimer’s disease (AD) is an irreversible progressive neurodegenerative disorder recognized by accumulation of amyloid-plaques (APs) and neurofibrillary tangles (NFTs) and eventually loss of memory. Glia maturation factor (GMF), a neuroinflammatory protein first time isolated and cloned in our laboratory plays an important role in the pathogenesis of AD. However, no studies have been reported on whether anti-GMF antibody administration could downregulate neuroinflammation and attenuate amyloid pathology in AD brain. We investigated the potential effect of single dose of (2 mg/kg b.wt/mouse) intravenously (iv) injected with anti-GMF antibodyon cognitive function, neuroprotection, neuroinflammation and Aβ load in the brain of 9-month-old 5XFAD mice. Following 4 weeks of anti-GMF antibody delivery in mice, we found reduced expression of GMF, astrocytic glial fibrillary acidic protein (GFAP) and microglial ionizing calcium binding adaptor molecule 1 (Iba1) as well as improvement inneuroinflammatory response via inhibition of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) production and amyloid pathology in the cerebral cortex and hippocampal CA1 region of 5XFAD mice. Correspondingly, blockade of GMF function with anti-GMF antibody improved spatial learning, memory, and long-term recognition memory in 5XFAD mice. The present study demonstrates that the immune checkpoint blockade of GMF function with anti-GMF antibody coordinates anti-inflammatory effects to attenuate neurodegeneration in the cortex and hippocampal CA1 region of 5XFAD mouse brain. Further, our data suggest, that pharmacological immune neutralization of GMF is a promising neuroprotective strategy totherapeutically target neuroinflammation and neurodegeneration in AD.

5XFAD mice Polyclonal anti-GMF antibody



中文翻译:

胶质细胞成熟因子的免疫抑制可逆转行为障碍,减轻阿尔茨海默病小鼠模型中的淀粉样斑块病理和神经炎症。

阿尔茨海默病 (AD) 是一种不可逆转的进行性神经退行性疾病,其特征是淀粉样斑块 (AP) 和神经原纤维缠结 (NFT) 的积累并最终丧失记忆力。神经胶质成熟因子(GMF)是我们实验室首次分离和克隆的一种神经炎症蛋白,在 AD 的发病机制中起着重要作用。然而,尚无关于施用抗 GMF 抗体是否可以下调 AD 脑中的神经炎症和减轻淀粉样蛋白病理的研究。我们研究了单剂量 (2 mg/kg b.wt/小鼠) 静脉内 (iv) 注射抗 GMF 抗体对 9 个月大 5XFAD 小鼠大脑中的认知功能、神经保护、神经炎症和 Aβ 负荷的潜在影响. 在小鼠体内递送抗 GMF 抗体 4 周后,我们发现 GMF 表达降低,星形胶质细胞纤维酸性蛋白 (GFAP) 和小胶质细胞电离钙结合接头分子 1 (Iba1) 以及通过抑制促炎细胞因子(TNF-α、IL-1β 和 IL-6)的产生和淀粉样蛋白病理学来改善神经炎症反应5XFAD 小鼠的大脑皮层和海马 CA1 区。相应地,用抗 GMF 抗体阻断 GMF 功能可改善 5XFAD 小鼠的空间学习、记忆和长期识别记忆。本研究表明,GMF 功能的免疫检查点阻断与抗 GMF 抗体协同抗炎作用,以减轻 5XFAD 小鼠大脑皮层和海马 CA1 区的神经变性。此外,我们的数据表明,

5XFAD小鼠多克隆抗GMF抗体

更新日期:2020-06-05
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